Risk of bleeding with ASA-Plavix combination

MATCH trial Diener et al. Took 7599 high risk patients with TIA or stroke, on Plavix, and added ASA 75 mg. Followed patients for 18 months. The results wre highly statistically significant with more major and minor bleeding of all types among patients receiving combination therapy. However, in the combined group, the actual risk of symptomatic intracranial hemorrhage was 1 % in each group; major bleeding of all types combined two percent v. one percent; and minor bleeding of all types combined was 3 % v. 1 %. Thus the overall complication rate is relatively low. The trial was based on the previous CURE trial that showed an acceptable safety profile of combined therapy among patients with acute coronary syndrome.

By contrast, the vascular risk reduction from antiplatelet therapy after TIA or stroke (reduction in stroke, MI or vascular death) was, absolute. 0.72 percent (NTT about 100/.72 or 138) with a relative risk reduction of 5.9 %. Thus by comparison the 3 % risk of hemorrhage is large.

OTHER EVIDENCE
CHARISMA trial supported results of MATCH.

CARESS trial in symptomatic carotid stenosis showed less embolic signals, but not less clinical events in patients on dual therapy.
FASTER trial suggested a role for dual therapy after clopidogrel loading for brief trial (90 days) after TIA. Not conclusive.

intravenous v intrarterial (bridging) lysis therapy

data of IMS investigators, reported in Stroke 2004. The outcomes overtly appear the same. Percent with modified Rankin of 0-1 at 90 days was 30 % in IMS group, 32 % in iv tpa group. The respective percentages for NIHSS less than 1 at 90 days was 28 and 25 %; Barthel index 95 or 100 46 and 42 %; these data favor intravenous therapy. However patients in the IMS trial were not equivalent at baseline. They had persistent major vascular occlusions despite early iv tpa treatment and greater clot burden than those in the NINDS trial, and were treated later. This suggests greater benefit in selected patients.